Chapter 15

1. Chapter 15 Reactions of Aromatic Compounds

2. Electrophilic AromaticSubstitution Reactions • Overall reaction:

4. A General Mechanism for Electro-philic Aromatic Substitution • Different chemistry with alkene.

5. Benzene does not undergo electrophilicaddition, but it undergoes electrophilic aromatic substitution.

6. Mechanism • Step 1:

7. Mechanism • Step 2:

8. Energy Profile for EAS:

9. Halogenation of Benzene • Benzene does not react with Br2 or Cl2 unless a Lewis acid is present (catalytic amount is usually enough) and the reaction typically requires heat.

10. Examples: • Reactivity: F2 > Cl2 > Br2 > I2

11. Mechanism:

12. Mechanism (Cont’d):

13. Mechanism (Cont’d):

14. F2: too reactive, give mixture of mono-, di- and highly substituted products.

15. I2: very unreactive even in the presence of Lewis acid, usually need to add an oxidizing agent (e.g. HNO3, Cu2+, H2O2).

16. Nitration of Benzene • Electrophile in this case is NO2 (nitronium ion).

17. Mechanism:

18. Mechanism (Cont’d):

19. Mechanism (Cont’d):

20. Sulfonation of Benzene • Mechanism • Step 1: • Step 2:

21. Step 3: • Step 4:

22. Sulfonation & Desulfonation: This is the only reversible EAS reaction.

23. Friedel–Crafts Alkylation • Electrophile in this case is R. • R = 2o or 3o • Or (R = 1o)

24. Mechanism:

25. Mechanism (Cont’d):

26. Mechanism (Cont’d):

27. Note: It is not necessary to start with an alkyl halide, other possible functional groups can be used to generate a reactive carbocation.

28. Examples:

29. Friedel–Crafts Acylation • Acyl group: • Electrophile in this case is R–C≡O (acylium ion).

30. Mechanism:

31. Mechanism (Cont’d):

32. Mechanism (Cont’d):

33. Acid chlorides (or acyl chlorides) • Can be prepared by:

34. Limitations of Friedel–CraftsReactions • When the carbocation formed from an alkyl halide, alkene, or alcohol can rearrange to one or more carbocations that are more stable, it usually does so, and the major products obtained from the reaction are usually those from the more stable carbocations.

35. (not formed) (How is this Formed?) • For example:

36. Reason: 1o cation (not stable) 3o cation (more stable)

37. Friedel–Crafts reactions usually give poor yields when powerful electron-withdrawing groups are present on the aromatic ring or when the ring bears an –NH2, –NHR, or –NR2 group. This applies to both alkylations and acylations, i.e. these do not work. These usually give poor yields in Friedel-Crafts reactions

38. The amino groups, –NH2, –NHR, and –NR2, are changed into powerful electron-withdrawing groups by the Lewis acids used to catalyze Friedel-Crafts reactions. Does not undergo a Friedel-Crafts reaction

39. Aryl and vinylic halides cannot be used as the halide component because they do not form carbocations readily. sp2 sp2

40. Polyalkylations often occur:

41. Synthetic Applications ofFriedel-Crafts Acylations: The Clemmensen Reduction • Clemmensen ketone reduction:

42. Clemmensen ketone reduction • A very useful reaction for making alkyl benzene that cannot be made via Friedel-Crafts alkylations.

43. Clemmensen ketone reduction • Cannot use Friedel-Crafts alkylation.

44. Rearrangements of carbon chain do not occur in Friedel-Crafts acylations. (no rearrangement of the R group)

45. FC Acylation followed by Clemmenson.

46. Substituents Can Affect Boththe Reactivity of the Ring and the Orientation of the Incoming Group • Two questions need to be addressed when the ring already has a substituent: • Reactivity toward EAS • Regiochemistry of products

47. Reactivity: faster or slower than Y = EDG (electron-donating group) or EWG (electron-withdrawing group).

48. Regiochemistry: Statistical mixture of o-, m-, p- products or any preference?

49. d+ d- Electrophilic reagent Arenium ion A substituted benzene

50. Z donates electrons Y withdraws electrons The ring is more electron rich and reacts faster with an electrophile The ring is electron poor and reacts more slowly with an electrophile